title: Gene-modified T lymphocytes in the setting of hematopoietic cell transplantation: potential benefits and possible risks.
abstract: BACKGROUND
  Allogeneic hematopoietic cell transplantation (HCT) is a consolidated treatment for several hematologic malignancies. Donor T lymphocytes can mediate a graft versus tumor (GVT) effect and control opportunistic infections but can also cause severe graft versus host disease (GVHD). Gene-transfer strategies are appealing tools to modulate T cell functions when infused after HCT.
  
  
  METHODS
  The current and potential future applications of T cell gene-transfer approaches to HCT. This review is not limited to GVHD control but covers the issues of GVT and immune reconstitution. Clinical data are used to discuss more general issues, perspectives and concerns common to gene-modification of T cells. An overview of the results and limitations emerging from clinical trials with herpes simplex virus-thymidine kinase (HSV-TK) engineered lymphocytes is provided. The review provides perspectives on additional gene-transfer strategies, currently at preclinical level or that have just entered clinical trials, to increase the efficacy and safety of HCT.
  
  
  CONCLUSIONS
  Gene-transfer can positively interfere with T cell functions after HCT. TK-lymphocytes have proven effective in controlling GVHD while retaining an acceptable GVT effect. Strategies exploiting new suicide molecules or engineered T cell receptors (TCRs) should be further explored to address current limitations with TK-lymphocytes and augment the efficacy and specificity of GVT and antiviral activity.
authors.affiliation: IRCC Institute for Cancer Research and Treatment, Laboratory of Cell Therapy, Department of Oncological Sciences, Strada Provinciale 142, Km 3.95, 10060 Candiolo, Turin, Italy. dario.sangiolo@ircc.it
authors.forename: Dario
authors.initials: D
authors.lastname: Sangiolo
authors.forename: Valeria
authors.initials: V
authors.lastname: Leuci
authors.forename: Susanna
authors.initials: S
authors.lastname: Gallo
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.forename: Wanda
authors.initials: W
authors.lastname: Piacibello
mesh_terms: D017209:Apoptosis / Q000235:genetics; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D013601:T-Lymphocytes / Q000378:metabolism*; D014161:Transduction, Genetic; D014162:Transfection